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Τετάρτη 15 Φεβρουαρίου 2017

Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates

Publication date: 14 February 2017
Source:Cell Reports, Volume 18, Issue 7
Author(s): Medya Mara Shikhagaie, Åsa K. Björklund, Jenny Mjösberg, Jonas S. Erjefält, Anne S. Cornelissen, Xavier Romero Ros, Suzanne M. Bal, Jasper J. Koning, Reina E. Mebius, Michiko Mori, Melanie Bruchard, Bianca Blom, Hergen Spits
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1+ group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1+ ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1+ ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1+ ILC3s. NRP1+ ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates.

Graphical abstract

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Teaser

Shikhagaie et al. find that NRP1 expressing human ILC3s are LTi-like cells, which are present in fetal tissues and adult lymphoid tissues, but not in peripheral blood or skin. NRP1+ ILC3s cells are primed and migrate in response to VEGF-A. In addition, their presence in the lungs of smokers and COPD patients provides insight into the formation of ectopic lymphoid aggregates.


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